Tissue-resident Macrophage Enhancer Landscapes Are Shaped by the Local Microenvironment
Yonit Lavin, Deborah Winter, Ronnie Blecher-Gonen, Eyal David 2, Hadas Keren-Shaul, Miriam Merad, Steffen Jung, Ido Amit
Macrophages are critical for innate immune defense and also control organ homeostasis in a tissue-specific manner. They provide a fitting model to study the impact of ontogeny and microenvironment on chromatin state and whether chromatin modifications contribute to macrophage identity. Here, we profile the dynamics of four histone modifications across seven tissue-resident macrophage populations. We identify 12,743 macrophage-specific enhancers and establish that tissue-resident macrophages have distinct enhancer landscapes beyond what can be explained by developmental origin. Combining our enhancer catalog with gene expression profiles and open chromatin regions, we show that a combination of tissue- and lineage-specific transcription factors form the regulatory networks controlling chromatin specification in tissue-resident macrophages. The environment is capable of shaping the chromatin landscape of transplanted bone marrow precursors, and even differentiated macrophages can be reprogrammed when transferred into a new microenvironment. These results provide a comprehensive view of macrophage regulatory landscape and highlight the importance of the microenvironment, along with pioneer factors in orchestrating identity and plasticity.
|Genomic assay||Bulk RNA-seq||Samples||Microglia, Kupffer cells, spleen, lung, peritoneal, ileal, colonic MFs and monocytes|
|Method for deriving gene sets||K-means||Number of gene sets||11|
|Figure source||Figure 1||Data source||Table S1|
Associated gene sets:
|Gene set #||Description||No. of genes|
|2||Kupffer cells & Spleen MΦ||287|
|3||Kupffer cells & Spleen & Lung MΦ||446|
|5||Lung & Peritoneal MΦ||177|
|7||Ileal & Colonic MΦ||276|
A total of 3004 genes are associated with this dataset.